Electro-Triggered Cascade Cyclization to Access Phosphinyl-Substituted N-Containing Heterocycles.

An electro-triggered cascade cyclization strategy was disclosed with concomitant phosphinylation and N-heterocycle construction. It provides a novel and environmentally friendly approach to access phosphinyl-substituted N-heterocycles with no external metal catalyst, oxidant, or heating. Mechanistic studies have revealed that anodic oxidation of H-phosphorus compounds occurs first to generate the key P-centered radical directly and cathodic reduction leads to the concurrent release of molecular hydrogen or methane. This protocol features simple operation, broad substrate scope, clean and mild conditions, and atom and step economy to form heterocycle-containing organophosphorus scaffolds.

Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss.

OBJECTIVE: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant management vs. preimplantation genetic diagnosis (PGD). DESIGN: Systematic review and meta-analysis. SETTING: Academic medical centers. PATIENT(S): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated. RESULT(S): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in couples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90-1.03; I2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I2 = 0). Compared with those who chose expectant management, differences in accumulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD. CONCLUSION(S): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management.

Fungal Diversity in the Soil of the Oxytropis glacialis Root System on the Qinghai-Tibet Plateau.

Because of swainonine-producing endophytic fungal, Oxytropis glacialis is one of the main poisonous weeds in the alpine grassland and desert grassland of the Qinghai-Tibet Plateau (QTP). It has a severe impact on grassland degradation on the QTP. In this manuscript, the Internally Transcribed Spacer (ITS) region of fungal communities in the soil of the O. glacialis root system was sequenced by high-throughput sequencing and analyzed by bioinformatics methods. The physical and chemical properties of the soil samples were analyzed in combination with the fungal diversity and its relationship with the soil physical and chemical factors. The results showed that the soil fungal community in the O. glacialis root system are rich in diversity in different ecological environments and are most affected by the soil pH value and organic matter. The swainonine-producing fungal Embellisia oxytropis was first detected in the soil of the O. glacialis root system. This finding provides data to support the next step in demonstrating the horizontal spread of swainone-producing fungal from O. glacialis to soil. In addition, a stable network of core flora has a facilitating effect on the formation of O. glacialis as a dominant species in alpine ecosystems.

HNF4A Regulates the Proliferation and Tumor Formation of Cervical Cancer Cells through the Wnt/ß-Catenin Pathway.

Hepatocyte nuclear factor 4 alpha (HNF4A) is a transcriptional factor which plays an important role in the development of the liver, kidney, and intestines. Nevertheless, its role in cervical cancer and the underlying mechanism remain unknown. In this study, both immunohistochemistry and western blotting revealed that the expression of HNF4A was downregulated in cervical cancer. Xenograft assays suggested that HN4A could inhibit tumorigenic potential of cervical cancer in vivo. Functional studies illustrated that HNF4A also inhibited the proliferation and viability of cervical cancer cells in vitro. In addition, FACS analysis implied that HNF4A could induce cell cycle arrest from the G0/G1 phase to S phase. Further studies suggested that HNF4A downregulated the activity of the Wnt/ß-catenin pathway. Altogether, our data demonstrated that HNF4A inhibited tumor formation and proliferation of cervical cancer cells through suppressing the activity of the Wnt/ß-catenin pathway.

LGR6 activates the Wnt/ß-catenin signaling pathway and forms a ß-catenin/TCF7L2/LGR6 feedback loop in LGR6high cervical cancer stem cells.

The leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is considered to be a stem cell marker in many normal tissues and promotes tissue development, regeneration, and repair. LGR6 is also related to the initiation and progression of some malignant tumors. However, the role of LGR6 in cervical cancer has not been reported. Here, immunohistochemistry and western blotting showed that LGR6 was significantly upregulated in cervical cancer, compared with the normal cervix. By analyzing The Cancer Genome Atlas database, LGR6 was found to be correlated with a poor prognosis of cervical cancer. Then, a small population of LGR6high cells isolated by using the fluorescence-activated cell sorting exhibited enhanced properties of cancer stem cells including self-renewal, differentiation, and tumorigenicity. Moreover, RNA sequencing revealed that LGR6 was correlated with the Wnt signaling pathway and TOP/FOP, reverse transcription-PCR, and western blotting further proved that LGR6 could activate the Wnt/ß-catenin signaling pathway. Interestingly, LGR6 upregulated the expression of TCF7L2 by activating the Wnt/ß-catenin pathway. Then, TCF7L2 combining with ß-catenin in the nucleus enhanced LGR6 transcription by binding the promoter of LGR6, which further activated the Wnt signaling to form a positive feedback loop. Thus, our study demonstrated that LGR6 activated a novel ß-catenin/TCF7L2/LGR6-positive feedback loop in LGR6high cervical cancer stem cells (CSCs), which provided a new therapeutic strategy for targeting cervical CSCs to improve the prognosis of cervical cancer patients.

[The Expression of CD40/CD40L in MM Patients and Its Significance to the Prognosis of MM Patients].

OBJECTIVE: To explore the expression of CD40/CD40L in multiple myeloma(MM) patients and its influence on prognosis. METHODS: Thirty patients with MM treated in Cangzhou People's Hospital from May 2016 to June 2017 were selected and divided into MM group, then 30 healthy people with a physical examination in our hospital at the same time were selected as the normal group. The serum CD40/CD40L levels of the patients in the two groups was detected by flow cytometry, and its correlation with the lymphocyte population, pathological grade and prognostic significance of MM patients was anaysis. RESULTS: The expression of CD40 in serum of the patients in MM group was significantly higher than those in normal group (P<0.05). The expression of CD40L in serum of the patients in MM group showed no significant difference as compared with those in normal group (P>0.05). The levels of CD40 and CD40L in the patients before and after chemotherapy showed no difference(P>0.05). The levels of Ts and NK cells in the patients of MM group were lower than those in normal group (P<0.05). The proportion of total B lymphocytes, Th and Th/Ts cells between the two groups showed no significant difference (P>0.05). The CD40 level was correlated with the serum total B lymphocyte level of the patients in MM group (r=0.877, P=0.005). There was a correlation with CD40L and Th cells in the serum of MM patients (r=-0.783, P=0.035). The expression of serum CD40 in the patients at phase III-IV was higher than those of the patients at phase I-II, the levels of serum CD40L in MM patients at different periods showed no significant difference(P>0.05). The survival rate of MM patients with high CD40 expression was lower than that of MM patients with low CD40 expression (χ2=1.639, P=0.201). The high level CD40 was the main factor affecting the prognosis of MM patients (95%CI: 1.156-4.125). CONCLUSION: The increasing of CD40 level in MM patients is related to the pathological grade of the patients. Chemotherapy can reduce the level of CD40. The increasing of CD40 is an important factor for the poor prognosis of MM patients. CD40L level is not meaningful for MM treatment and prognosis.

Genetic Characteristics and Antimicrobial Susceptibility of Arcobacter butzleri Isolates from Raw Chicken Meat and Patients with Diarrhea in China.

Arcobacter is an emerging foodborne pathogen worldwide. In this study, the prevalence, antimicrobial susceptibility and genetic characteristics of Arcobacter from different sources were investigated. Eighteen A. butzleri isolates were obtained from 60 raw chicken meat samples (16/60, 27%) and 150 patients with diarrhea (2/150, 1.3%). The resistance ratios to nalidixic acid, ciprofloxacin, clindamycin, chloramphenicol, and florfenicol were 83.33% (15/18), 38.89% (7/18), 38.89% (7/18), 33.33% (6/18) and 33.33% (6/18), respectively. We performed whole genome sequencing of the 18 isolates, and we predicted antibiotic resistance genes and virulence factors by using assembled genomes through blastx analysis. Two resistance genes, bla OXA-464 and tet(H), and the C254T mutation in gyrA, were identified in the genomes of some resistant isolates. Furthermore, virulence genes, such as flgG, flhA, flhB, fliI, fliP, motA, cadF, cjl349, ciaB, mviN, pldA and tlyA, were found in all strains, whereas hecA, hecB and iroE were found in only some strains. Phylogenetic tree analysis of A. butzleri isolates on the basis of the core-genome single nucleotide polymorphisms showed that two isolates from patients with diarrhea clustered together, separately from the isolates from raw chicken and the chicken strains. This study is the first comprehensive analysis of Arcobacter isolated in Beijing.

Hexokinase 2 Promotes Cell Growth and Tumor Formation Through the Raf/MEK/ERK Signaling Pathway in Cervical Cancer.

Hexokinase 2 (HK2) is a member of the hexokinases (HK) that has been reported to be a key regulator during glucose metabolism linked to malignant growth in many types of cancers. In this study, stimulation of HK2 expression was observed in squamous cervical cancer (SCC) tissues, and HK2 expression promoted the proliferation of cervical cancer cells in vitro and tumor formation in vivo by accelerating cell cycle progression, upregulating cyclin A1, and downregulating p27 expression. Moreover, transcriptome sequencing analysis revealed that MAPK3 (ERK1) was upregulated in HK2-overexpressing HeLa cells. Further experiments found that the protein levels of p-Raf, p-MEK1/2, ERK1/2, and p-ERK1/2 were increased in HK2 over-expressing SiHa and HeLa cells. When ERK1/2 and p-ERK1/2 expression was blocked by an inhibitor (FR180204), reduced cyclin A1 expression was observed in HK2 over-expressing cells, with induced p27 expression and inhibited cell growth. Therefore, our data demonstrated that HK2 promoted the proliferation of cervical cancer cells by upregulating cyclin A1 and down-regulating p27 expression through the Raf/MEK/ERK signaling pathway.

NF-YA promotes the cell proliferation and tumorigenic properties by transcriptional activation of SOX2 in cervical cancer.

NF-YA is considered as a crucial regulator for the maintenance of cancer stem cell (CSC) and involved in various types of malignant tumours. However, the exact function and molecular mechanisms of NF-YA in the progression of cervical cancer remains poorly understood. Here, the expression of NF-YA detected by immunohistochemistry was gradually increased from normal cervical tissues, to the high-grade squamous intraepithelial lesions, and then to cervical cancer tissues. NF-YA promoted the cell proliferation and tumorigenic properties of cervical cancer cells as well as tumorsphere formation and chemoresistance in vitro. The luciferase reporter assay combined with mutagenesis analyses and Western blotting showed that NF-YA trans-activated the expression of SOX2 in cervical cancer. Furthermore, quantitative chromatin immunoprecipitation (qChIP) and electrophoretic mobility shift assay (EMSA) confirmed that NF-YA protein directly bound to the CCAAT box region located upstream of the SOX2 promoter. Together, our data demonstrated that NF-YA was highly expressed in cervical cancer and promoted the cell proliferation, tumorigenicity and CSC characteristic by trans-activating the expression of SOX2.

HOXA5 inhibits the proliferation and neoplasia of cervical cancer cells via downregulating the activity of the Wnt/ß-catenin pathway and transactivating TP53.

HOXA5 is considered a regulator involved in embryonic development and cellular differentiation and a tumor suppressor. Nevertheless, its biological role in cervical carcinoma is still unclear. In the present study, immunohistochemistry showed that HOXA5 expression gradually decreased as the degree of cervical lesions deepened. Ectopic expression of HOXA5 restrained cell proliferation, decreased cell viability, and inhibited tumor formation in vitro and in vivo. Furthermore, the expression of HOXA5 could arrest cell cycle from G0/G1 to S phase. RNA-seq revealed that p21 and cyclinD1 were involved in this process. Moreover, the gene set enrichment analysis and the TOP/FOP reporter assay both suggested that HOXA5 could restrain the activity of the Wnt/ß-catenin pathway. Further study using dual-luciferase reporter assay and quantitative chromatin immunoprecipitation assay demonstrated that HOXA5 could directly bind to the TAAT motif within the promoter of TP53 by its HD domain and transactivate TP53, which can upregulate p21. Altogether, our data suggest that HOXA5 inhibits the proliferation and neoplasia via repression activity of the Wnt/ß-catenin pathway and transactivating TP53 in cervical cancer.

[Establishing potential habitats of Mytilopsis sallei with Maxent niche model]. / 应用Maxent建立沙筛贝潜在生境模型.

Mytilopsis sallei, an invasive alien species, has strong reproductive ability and high adaptability. It can severely endanger biodiversity of intertidal ecosystem after invasion. The intertidal zones and oyster breeding areas in some coastal areas of Guangdong Province have been severely invaded by M. sallei. To examine the potential habitat of M. sallei in China, we established a potential habitat prediction model of M. sallei using Maxent and ArcGIS method for China and global scales. The model was verified by the method of receiver operating characteristic curve (ROC) analysis and field investigation. The results showed that M. sallei could distribute with high probabili-ty in the area between North and South America, South India in Asia, Sri Lanka, the south coast of the Yangtze River in China, and in Van Dimen Bay of the southern hemisphere. In China, M. sallei mainly distributed in coastal provinces south of Shanghai. The main environmental factors affecting the suitable distribution areas for M. sallei were water vapor pressure, temperature, and solar radiation. After ROC detection, the AUC values of both the training and testing sets were 0.996, indicating that the prediction reached an excellent level. Our results provide theoretical basis for the risk assessment and management of M. sallei, and complement the potential habitat prediction of invasive species in China.

Effect of a Dual Functional Polymer on the Electro-Optical Properties of Blue Phase Liquid Crystals.

The effects of the fluorinated monomer with an ethynyl group on the electro-optical properties of polymer-stabilized blue phase liquid crystals (PSBPLCs) were investigated in different polymer systems. In rigid polymer systems, the Kerr constant can be increased by about 27.6%, while keeping a microsecond response time. In soft polymer systems, hysteresis decreased by about 45.5% and residual birefringence can be reduced from 1.85% to 0.6%. The above phenomena exhibited dual functions of affecting the anchoring energy and the viscosity of the system simultaneously. The results provide a potential value for the ethynyl-containing monomers in PSBPLC systems.

[Improved temporary and treatment partial denture in the rehabilitation of patients with temporomandibular joint disorder syndrome].

OBJECTIVE: This study aims to study the effect of the improved partial denture treatment in the rehabilitation of patients with temporomandibular joint disorders (TMD). METHODS: Twenty middle-aged and old patients suffering from osteoarthrosis were treated with the improved partial denture treatment. These patients were followed up during the partial denture treatment and after the rehabilitation. Both the clinical symptoms and Fricton's craniomandibular index were used to evaluate the clinical effects. Data were analyzed using SPSS17.0. RESULTS: The effective rate reached 100% when the patients wore partial dentures for 1 month. All of the 20 patients were comfortable with temporomandibular joint, and they expressed ultimate satisfaction with the denture. The Fricton indexes of 20 patients decreased significantly after the treatment (P<0.05). CONCLUSIONS: Partial denture treatment is an ideal method in rehabilitation for patients with TMD (osteoarthrosis) and dentition defect.

The observed difference of RAW264.7 macrophage phenotype on mineralized collagen and hydroxyapatite.

Understanding the interaction between biomaterials and the immune system has become increasingly important. Mineralized collagen (MC) has the same chemical components and microstructures to natural bone tissue, and is considered as a better biomaterial for bone prostheses compared to hydroxyapatite (HA). However, there is little information about how MC affects inflammatory responses. In this study, we investigate the inflammatory responses to MC and HA by culturing RAW264.7 cells on their surfaces. We observed that MC increases CD206+ staining and IL-10 (M2 macrophages), whereas HA shows cells expressing more CD86 and secreting more TNF-α. This result indicates that MC may attenuate inflammatory responses to implanted bone prostheses.

Tick-Borne Pathogens in Ixodid Ticks from Poyang Lake Region, Southeastern China.

Ticks are the vectors of various pathogens, threatening human health and animal production across the globe. Here, for the first time we detected Ricketssia spp., Borrelia spp. and protozoan in ticks from Poyang Lake region in Ji- angxi Province of eastern China. In 3 habitat categories and on 12 host species, 311 ticks from 11 species were collected. Haemaphysalis longicornis was the predominant species, accounting for 55.63%, followed by Rhipicephalus microplus, Haemaphysalis flava and Ixodes granulatus. Of the collected ticks, 7.07% were positive for tick-borne pathogens, and H. longicornis and H. flava were found to be co-infected with Ricketssia spp. and protozoan. H. flava was the most detected positive for tick-borne pathogens, whereas H. longicornis had the lowest infection rate, and the difference in infection rates between tick species was significant (χ2=61.24, P<0.001). Furthermore, adult ticks demonstrated remarkably greater infection rate than immature ticks (χ2=10.12, P=0.018), meanwhile ticks on Erinaceidae showed significantly higher positivity than ticks collected on other host species (χ2=108.44, P<0.001). Genetic fragment sequencing and analyses showed at least 4 pathogen species presence in ticks, namely Borrelia yangtzensis, Rickettsia slovaca or Rickettsia raoultii related genospecies, Babesia vogeli and Hepatozoon canis or Hepatozoon felis related genospecies. The finding indicates that the abundant ticks can carry diverse pathogens in Poyang Lake region, and pathogen infection is highly related to species, vertebrate hosts and life stages of ticks.

[The improvement of periodontal teaching mode based on PDCA theory].

PURPOSE: To evaluate the effect of PDCA teaching mode on clinical ability in the process of periodontal clinical internship. METHODS: Forty-eight undergraduate interns coming from School of Stomatology, China Medical University were divided into 2 groups, one group received traditional teaching mode, the other group received a teaching mode based on PDCA cycle. At the end of internship, every student was assessed by theoretical examinations, case reports and clinical skill practice. χ2-test was used to determine the significant difference in clinical ability between the two groups. Statistical analysis was carried out using SPSS 13.0 software package. RESULTS: In clinical skill examination, 17 students in PDCA teaching mode group got "excellent" grade , 8 students got "good" grade, none student got "passed" grade; in traditional teaching mode group, 7 students got "excellent" grade, 16 students got "good" grade, 1 student got "passed" grade. The difference between the two groups was statistically significant (P<0.05). In the theoretical examinations and case reports, 16 students in PDCA teaching mode group got "excellent" grade, 8 students got "good" grade, none student got "passed" grade; in traditional teaching mode group, 12 students got "excellent" grade, 9 students got "good" grade, and 3 students got "passed" grade. The difference between the two groups wasn't statistically significant (P>0.05). CONCLUSIONS: PDCA teaching will train each student in a personalized mode, which is beneficial to finding defects existed in clinical practice and reinforcing the ability of communication and clinical practice.

Effects of losses in the atom-light hybrid SU(1,1) interferometer.

Collective atomic excitation can be realized by the Raman scattering. Such a photon-atom interface can form an SU(1,1)-typed atom-light hybrid interferometer, where the atomic Raman amplification processes take the place of the beam splitting elements in a traditional Mach-Zehnder interferometer. We numerically calculate the phase sensitivities and the signal-to-noise ratios (SNRs) of this interferometer with the method of homodyne detection and intensity detection, and give their differences of the optimal phase points to realize the best phase sensitivities and the maximal SNRs from these two detection methods. The difference of the effects of loss of light field and atomic decoherence on measure precision is analyzed.

A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa.

A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.

Efficacy of Cranial Electrotherapy Stimulation Combined with Biofeedback Therapy in Patients with Functional Constipation.

BACKGROUND/AIMS: A large number of studies have shown that function constipation (FC) has an extremely high incidence of mental and psychological disorders. Cranial electrotherapy stimulation (CES) was applied to the treatment of psychological disorders such as anxiety and depression. We explored the effects of CES combined with biofeedback therapy (BFT) on the psychological state, clinical symptoms, and anorectal function in patients with FC. METHODS: A total of 74 patients with FC were randomly divided into 2 groups. The control group received BFT. CES combined with BFT was carried out in the experiment group. All patients were assessed using the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Wexner constipation score at baseline and the end of each course. Anorectal manometry and balloon expulsion tests were performed before and after treatment. RESULTS: After treatment, the participants in the experiment group had significantly lower score SAS, SDS, and Wexner constipation scores than the control group (all P < 0.05). The number of successful expulsion in the experiment group was larger than the control group (P = 0.016). CONCLUSIONS: CES combined with BFT was effective in improving the psychological status of anxiety, depression, and bowel symptoms in patients with FC.

Sequence variation of Bemisia tabaci Chemosensory Protein 2 in cryptic species B and Q: New DNA markers for whitefly recognition.

Bemisia tabaci Gennadius biotypes B and Q are two of the most important worldwide agricultural insect pests. Genomic sequences of Type-2 B. tabaci chemosensory protein (BtabCSP2) were cloned and sequenced in B and Q biotypes, revealing key biotype-specific variations in the intron sequence. A Q260 sequence was found specifically in Q-BtabCSP2 and Cucumis melo LN692399, suggesting ancestral horizontal transfer of gene between the insect and the plant through bacteria. A cleaved amplified polymorphic sequences (CAPS) method was then developed to differentiate B and Q based on the sequence variation in exon of BtabCSP2 gene. The performances of CSP2-based CAPS for whitefly recognition were assessed using B. tabaci field collections from Shandong Province (P.R. China). Our SacII based CAPS method led to the same result compared to mitochondrial cytochrome oxidase-based CAPS method in the field collections. We therefore propose an explanation for CSP origin and a new rapid simple molecular method based on genomic DNA and chemosensory gene to differentiate accurately the B and Q whiteflies of the Bemisia complex around the world.